February 16, 2022
UNC Eshelman School of Pharmacy’s Marina Sokolsky-Papkov, Ph.D., and Timothy Gershon, MD, Ph.D., of the UNC School of Medicine, have discovered a combination therapy to treat medulloblastoma – a brain tumor more commonly diagnosed in children.
In the United States, there are more than 3,800 people living with the fast-growing disease, according to the National Cancer Institute.
“Patients with medulloblastoma, the most common malignant brain tumor in children, need new therapies,” Sokolsky-Papkov said. “The current standard treatment for medulloblastoma with surgery, craniospinal radiation, and chemotherapy cures about 80% of patients, but causes disabling long-term effects, including neurocognitive impairment, hearing loss, endocrine dysfunction, and secondary malignancies. Survivors remain at risk of recurrence after treatment, and recurrent medulloblastoma is presently incurable.”
Sokolsky-Papkov, a research assistant professor in the School’s Division of Pharmacoengineering and Molecular Pharmaceutics, partnered with Gershon to help patients, particularly children, who are battling the disease. Their work, recently published in Science Advances is titled, “Enhancing CDK4/6 inhibitor therapy for medulloblastoma using nanoparticle delivery and scRNA-seq–guided combination with sapanisertib.”
The published work highlights that palbociclib, a drug FDA-approved for breast cancer, may be effective for medulloblastoma when combined with a mTOR inhibitor drug called sapanisertib.
“Palbociclib has been suggested for brain tumors, but it has typically failed to be curative because it does not stay in the brain for long and because tumors become resistant to it,” Sokolsky-Papkov said.
The research team addressed the limited brain concentrations of the drug by developing a nanoparticle formulation that gets into the brain more effectively. They also studied resistance using single-cell RNA-seq technology. In doing so, they found a mechanism of resistance they could target with another drug, sapanisertib.
The team then used nanoparticle co-loaded with palbociclib and sapanisertib and found that mice with medulloblastoma lived longer when treated with the combination therapy compared to either drug alone.
“Our results can be generalized, and we argue in the paper that children with medulloblastoma who need new therapies should be treated with our combination,” Sokolsky-Papkov said. “This could be life-changing for patients.”
Additional authors on the published work include: Chaemin Lim, Taylor Dismuke, Daniel Malawsky, Jacob D. Ramsey, Duhyeong Hwang, Virginia L. Godfrey, and Alexander V. Kabanov.
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